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Ischemic preconditioning and preinfarction angina in the clinical arena

Nature Clinical Practice Cardiovascular Medicine volume 1, pages 96–102 (2004)Cite this article

Abstract

In animals, brief episodes of ischemia before a total coronary occlusion protect the heart and result in a smaller myocardial infarct size. In humans, episodes of angina before acute myocardial infarction might also confer a preconditioning or protective effect; numerous studies show that preinfarction angina is associated with smaller infarcts. Preinfarction angina is also associated with reductions in ventricular dysfunction, arrhythmias and incidence of no-reflow phenomena, and, in some cases, improved survival. The protective effect of preconditioning in humans is characterized by marked individual variations and seems to be attenuated in women, people with diabetes and the elderly. Exercise seems to be an important way to induce preconditioning in humans and preserves it in the elderly.

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References

  1. Kloner RA and Yellon D (1994) Does ischemic preconditioning occur in patients? J Am Coll Cardiol 24: 1133–1142

    Article  CAS  Google Scholar 

  2. Jaffe MD and Quinn NK (1980) Warm-up phenomenon in angina pectoris. Lancet 2: 934–936

    Article  CAS  Google Scholar 

  3. Lange R et al. (1984) Effects of recurrent ischemia on myocardial high energy phosphate content in canine hearts. Basic Res Cardiol 79: 469–478

    Article  CAS  Google Scholar 

  4. Murry CE et al. (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74: 1124–1136

    Article  CAS  Google Scholar 

  5. Przyklenk K and Kloner RA (1998) Ischemic preconditioning: exploring the paradox. Prog Cardiovasc Dis 40: 517–547

    Article  CAS  Google Scholar 

  6. Bolli R (2000) The late phase of preconditioning. Circ Res 87: 972–983

    Article  CAS  Google Scholar 

  7. Takaoka A et al. (1999) Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of “remote preconditioning”. J Am Coll Cardiol 33: 556–564

    Article  CAS  Google Scholar 

  8. Fowler NO (1971) “Preinfarctional” angina. A need for an objective definition and for a controlled clinical trial of its management. Circulation 44: 755–758

    Article  CAS  Google Scholar 

  9. Kloner RA and Jennings RB (2001) Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. Circulation 104: 2981–2989

    Article  CAS  Google Scholar 

  10. Kloner RA and Jennings RB (2001) Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation 104: 3158–3167

    Article  CAS  Google Scholar 

  11. Laskey WK and Beach D (1994) Frequency and clinical significance of ischemic preconditioning during percutaneous coronary intervention. J Am Coll Cardiol 42: 998–1003

    Article  Google Scholar 

  12. Kloner RA et al. (1995) Previous angina alters in-hospital outcome in TIMI 4. A clinical correlate to preconditioning? Circulation 91: 37–45

    Article  CAS  Google Scholar 

  13. Kloner RA et al. (1998) Prospective temporal analysis of the onset of preinfarction angina versus outcome: an ancillary study in TIMI-9B. Circulation 97: 1042–1045

    Article  CAS  Google Scholar 

  14. Ottani F et al. (1995) Prodromal angina limits infarct size. A role for ischemic preconditioning. Circulation 91: 291–297

    Article  CAS  Google Scholar 

  15. Anzai T et al. (1995) Preinfarction angina as a major predictor of left ventricular function and long-term prognosis after a first Q wave myocardial infarction. J Am Coll Cardiol 26: 319–327

    Article  CAS  Google Scholar 

  16. Zahn R et al. (2001) Effect of preinfarction angina pectoris on outcome in patients with acute myocardial infarction treated with primary angioplasty (results from the Myocardial Infarction Registry [MIR]). Am J Cardiol 87: 1–6

    Article  CAS  Google Scholar 

  17. Fujita M et al. (1999) Determinants of collateral development in patients with acute myocardial infarction. Clin Cardiol 22: 595–599

    Article  CAS  Google Scholar 

  18. Perez-Castellano N et al. (1998) Influence of collateral circulation on in-hospital death from anterior acute myocardial infarction. J Am Coll Cardiol 31: 512–518

    Article  CAS  Google Scholar 

  19. Yamagishi H et al. (2000) Effects of preinfarction angina on myocardial injury in patients with acute myocardial infarction: a study with resting 123I-BMIPP and 201T1 myocardial SPECT. J Nucl Med 41: 830–836

    CAS  PubMed  Google Scholar 

  20. Andreotti F et al. (1996) Preinfarction angina as a predictor of more rapid coronary thrombolysis in patients with acute myocardial infarction. N Engl J Med 334: 7–12

    Article  CAS  Google Scholar 

  21. Migrino RQ et al. (1996) Preinfarction angina. N Engl J Med 335: 59–61

    Article  CAS  Google Scholar 

  22. O'Rourke B (2004) Evidence for mitochondrial K+ channels and their role in cardioprotection. Circ Res 94: 420–432

    Article  CAS  Google Scholar 

  23. Napoli C et al. (1998) New-onset angina preceding acute myocardial infarction is associated with improved contractile recovery after thrombolysis. Eur Heart J 19: 411–419

    Article  CAS  Google Scholar 

  24. Noda T et al. (1999) Evidence for the delayed effect in human ischemic preconditioning: prospective multicenter study for preconditioning in acute myocardial infarction. J Am Coll Cardiol 34: 1966–1974

    Article  CAS  Google Scholar 

  25. Neskovic AN et al. (2001) Preinfarction angina prevents left ventricular remodeling in patients treated with thrombolysis for myocardial infarction. Clin Cardiol 24: 364–370

    Article  CAS  Google Scholar 

  26. Iglesias-Garriz I et al. (2001) Pre-infarction angina elicits greater myocardial viability on reperfusion after myocardial infarction: a dobutamine stress echocardiographic study. J Am Coll Cardiol 37: 1846–1850

    Article  CAS  Google Scholar 

  27. Hirai T et al. (1992) Significance of preinfarction angina for preservation of left ventricular function in acute myocardial infarction. Am Heart J 124: 19–24

    Article  CAS  Google Scholar 

  28. Rezkalla SH and Kloner RA (2002) No-reflow phenomenon. Circulation 105: 656–662

    Article  Google Scholar 

  29. Yip HK et al. (2002) Angiographic morphologic features of infarct-related arteries and timely reperfusion in acute myocardial infarction: predictors of slow-flow and no-reflow phenomenon. Chest 122: 1322–1332

    Article  Google Scholar 

  30. Takahashi T et al. (2000) Absence of preinfarction angina is associated with a risk of no-reflow phenomenon after primary coronary angioplasty for a first anterior wall acute myocardial infarction. Int J Cardiol 75: 253–260

    Article  CAS  Google Scholar 

  31. Colonna P et al. (2002) Reduced microvascular and myocardial damage in patients with acute myocardial infarction and preinfarction angina. Am Heart J 144: 796–803

    Article  Google Scholar 

  32. Taggart P and Yellon DM (2002) Preconditioning and arrhythmias. Circulation 106: 2999–3001

    Article  Google Scholar 

  33. Li YW et al. (1992) The transient nature of the effect of ischemic preconditioning on myocardial infarct size and ventricular arrhythmia. Am Heart J 123: 346–353

    Article  CAS  Google Scholar 

  34. Gheeraert PJ et al. (2001) Preinfarction angina protects against out-of-hospital ventricular fibrillation in patients with acute occlusion of the left coronary artery. J Am Coll Cardiol 38: 1369–1374

    Article  CAS  Google Scholar 

  35. Pasceri V et al. (1996) Preconditioning by transient myocardial ischemia confers protection against ischemia-induced ventricular arrhythmias in variant angina. Circulation 94: 1850–1856

    Article  CAS  Google Scholar 

  36. Wu ZK et al. (2002) Ischemic preconditioning suppresses ventricular tachyarrhythmias after myocardial revascularization. Circulation 106: 3091–3096

    Article  Google Scholar 

  37. Wu ZU et al. (2003) Fibrillation in patients subjected to coronary artery bypass grafting. J Thorac Cardiovasc Surg 126: 1477–1482

    Article  Google Scholar 

  38. Carr-White G et al. (2004) Chronic stable ischaemia protects against myocyte damage during beating heart coronary surgery. Eur J Cardiothorac Surg 25: 772–778

    Article  Google Scholar 

  39. Shiraki H et al. (1998) Association between preinfarction angina and a lower risk of right ventricular infarction. N Engl J Med 338: 941–947

    Article  CAS  Google Scholar 

  40. Abete P et al. (1997) Angina-induced protection against myocardial infarction in adult and elderly patients: a loss of preconditioning mechanism in the aging heart? J Am Coll Cardiol 30: 947–954

    Article  CAS  Google Scholar 

  41. Kloner RA et al. (1998) Protection conferred by preinfarct angina is manifest in the aged heart: evidence from the TIMI 4 trial. J Thromb Thrombolysis 6: 89–92

    Article  CAS  Google Scholar 

  42. Jimenez-Navarro M et al. (2002) Cardioprotective effects of preinfarction angina in elderly: same patients, different results? Am J Cardiol 89: 651

    Article  Google Scholar 

  43. Abete P et al. (2001) High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients. J Am Coll Cardiol 38: 1357–1365

    Article  CAS  Google Scholar 

  44. Miki T et al. (1996) Captopril potentiates the myocardial infarct size-limiting effect of ischemic preconditioning through bradykinin B2 receptor activation. J Am Coll Cardiol 28: 1616–1622

    Article  CAS  Google Scholar 

  45. Hill M et al. (2001) Nitroglycerin induces late preconditioning against myocardial infarction in conscious rabbits despite development of nitrate tolerance. Circulation 104: 694–699

    Article  CAS  Google Scholar 

  46. Zhang ZW et al. (2001) Ischemic preconditioning and nicorandil pretreatment improve donor heart preservation. Jpn Circ J 65: 678–682

    Article  CAS  Google Scholar 

  47. Domenech R et al. (2002) Exercise induces early and late myocardial preconditioning in dogs. Cardiovasc Res 55: 561–566

    Article  CAS  Google Scholar 

  48. Zdrenghea D et al. (1998) Ischemic preconditioning during successive exercise testing. Rom J Intern Med 36: 161–165

    CAS  PubMed  Google Scholar 

  49. Lambiase PD et al. (2003) Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment. J Am Coll Cardiol 41: 1174–1182

    Article  Google Scholar 

  50. Anzai T et al. (1994) Effect on short-term prognosis and left ventricular function of angina pectoris prior to first Q-wave anterior wall acute myocardial infarction. Am J Cardiol 74: 755–759

    Article  CAS  Google Scholar 

  51. Nakagawa Y et al. (1995) Effect of angina pectoris on myocardial protection in patients with reperfused anterior wall myocardial infarction: retrospective clinical evidence of “preconditioning”. J Am Coll Cardiol 25: 1076–1083

    Article  CAS  Google Scholar 

  52. Ishihara M et al. (1997) Implications of prodromal angina pectoris in anterior wall acute myocardial infarction: acute angiographic findings and long-term prognosis. J Am Coll Cardiol 30: 970–975

    Article  CAS  Google Scholar 

  53. Tomoda H and Aoki N (1999) Comparison of protective effects of preinfarction angina pectoris in acute myocardial infarction treated by thrombolysis versus by primary coronary angioplasty with stenting. Am J Cardiol 84: 621–625

    Article  CAS  Google Scholar 

  54. Iglesias-Garriz I et al. (2000) The effect of pre-infarction unstable angina on the size of myocardial necrosis. Rev Esp Cardiol 53: 43–48

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Thanks to Linda Weis and Alice Stargardt, Marshfield Clinic Research Foundation, for assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Cardiovascular Research, Marshfield Clinic, Marshfield, WI

    Shereif H Rezkalla

  2. University of Wisconsin, Madison, WI, USA

    Shereif H Rezkalla

  3. Heart Institute, Good Samaritan Hospital,

    Robert A Kloner

  4. Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Robert A Kloner

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  1. Shereif H Rezkalla
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Correspondence to Shereif H Rezkalla.

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Rezkalla, S., Kloner, R. Ischemic preconditioning and preinfarction angina in the clinical arena. Nat Rev Cardiol 1, 96–102 (2004). https://doi.org/10.1038/ncpcardio0047

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